The objective of this proposal is to substantially enhance the sequencing capabilities of the established and highly productive Genome Technology Core (GTC) at Vanderbilt University Medical Center through the acquisition of an Illumina Genome Analyzer IIx next-generation DNA sequencer. The GTC was founded in 2008 as an institutional core facility managed by the Office of Personalized Medicine and tasked with supporting the genomic needs of Vanderbilt investigators and their collaborators. A single Illumina Genome Analyzer instrument, necessary staff and secondary equipment were purchased or supported with institutional funds. Since its founding, the GTC has swiftly implemented a number of technologies and applications to establish a reliable and robust high-performance sequencing service. The rapid success of this effort has resulted in the near full utilization of our single instrument leading to long wait times for new projects. This application has been developed to address two vital issues identified by the staff of the GTC. First, the major users listed in this application represent a group of heavy users of the proposed instrument (more than 75% projected utilization for 3 years) that are not currently being supported, underscoring the need for additional sequencing capacity. Second, many investigators are utilizing paired end and longer read length sequencing runs to achieve higher sequencing coverage for each sample. These longer reads and paired end approaches require substantially longer instrument run times, putting further pressure on the existing instrumentation. Together, these issues provide a strong justification for this application to support an additional Illumina instrument in the GTC. The GTC has been extremely successful in supporting a diverse group of investigators that have made use of the existing instrumentation and in implementing and optimizing technical protocols and bioinformatic tools on the Illumina platform. This success will be further enhanced by the additional instrumentation to allow the GTC to efficiently support a larger group of NIH funded investigators. The continued success of the GTC will be assured by the strong institutional commitments, and extremely proficient bioinformatic capabilities.